KR101302163B1 - Pharmaceutical composition for prevention and treatment of dementia, Parkinson's disease or epilepsy comprising extracts of Houttuynia cordata THUNB. as an active ingredient - Google Patents
Pharmaceutical composition for prevention and treatment of dementia, Parkinson's disease or epilepsy comprising extracts of Houttuynia cordata THUNB. as an active ingredient Download PDFInfo
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- KR101302163B1 KR101302163B1 KR1020110104179A KR20110104179A KR101302163B1 KR 101302163 B1 KR101302163 B1 KR 101302163B1 KR 1020110104179 A KR1020110104179 A KR 1020110104179A KR 20110104179 A KR20110104179 A KR 20110104179A KR 101302163 B1 KR101302163 B1 KR 101302163B1
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Abstract
본 발명은 어성초(Houttuynia cordata THUNB.) 추출물을 유효성분으로 함유하는 치매(dementia), 파킨슨병(Parkinson's disease) 또는 간질(epilepsy) 예방 및 치료용 약학적 조성물에 관한 것으로, 보다 상세하게는 본 발명의 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물은 베타아밀로이드(Amyloid-β) 유발 치매 모델에서 세포 보호효과 및 인지기능 개선 효과를 나타내고, 6-OHDA(6-hydroxydopamine) 유발 파킨슨병 모델에서 세포보호 효과를 가지며, 카인산(Kainic acid) 유발 간질 모델에서 세포 보호효과 및 인지기능 개선 효과를 나타냄으로써, 치매, 파킨슨병 또는 간질 예방 및 치료용 약학적 조성물 또는 상기 목적의 건강식품으로 유용하게 사용될 수 있다. The present invention relates to a method for the treatment of Houttuynia The present invention relates to a pharmaceutical composition for the prevention and treatment of dementia, Parkinson's disease or epilepsy containing an extract of cordata THUNB. as an active ingredient, and more particularly to a pharmaceutical composition for preventing and treating dementia, Parkinson's disease or epilepsy, The mixture of extracts and Glycyrrhiza uralensis shows cytoprotective and cognitive functions in the amyloid-β induced dementia model, has cytoprotective effect in 6-OHDA (6-hydroxydopamine) induced Parkinson's disease model, (Kainic acid) -induced epilepsy model, it can be effectively used as a pharmaceutical composition for the prevention and treatment of dementia, Parkinson's disease or epilepsy, or as a health food for the above-mentioned purpose.
Description
본 발명은 생약재 추출물 또는 이의 혼합물을 유효성분으로 함유하는 치매(dementia), 파킨슨병(Parkinson's disease) 또는 간질(epilepsy) 예방 및 치료용 약학적 조성물 또는 건강식품용 조성물에 관한 것이다.
The present invention relates to a pharmaceutical or health food composition for preventing and treating dementia, Parkinson's disease or epilepsy containing an extract of herbal medicine or a mixture thereof as an active ingredient.
통계청에서 2003년 10월 발표한 우리나라 노령 인구의 비율을 살펴보면, 우리나라는 지난 2000년 65세 이상 인구가 총인구에서 차지하는 비중이 7.2%에 이르러 고령화 사회에 들어섰으며, 오는 2019년에서는 이 비율이 14%를 넘어 고령사회에 진입할 것으로 전망되고 있다. 이와 같이 고령화 문제가 사회적인 이슈로 대두 됨에 따라 고령인구의 특성이나 주거, 보건, 문화, 여가 등 노인복지 등에 대한 국민의 관심이 높아지고, 이에 대한 통계 수요도 늘어나고 있다. 이러한 변화의 핵심은 노령화 인구의 증가로 인해서 지난 50여 년간 사망의 주된 원인이 되었던 급성 전염성 질병보다도 만성 퇴행성 질병이 더욱더 큰 문제로 대두 되고 있다는 점이다. 특히 만성 퇴행성 질병 중에서 뇌혈관 질환에 의한 사망은 단일질환에 의한 사망률 중에서 2위를 기록하고 있는 매우 중요한 질환이다.
According to the National Statistical Office (NSO), the percentage of the elderly population in Korea is as follows: In 2000, the proportion of the population aged 65 and over accounted for 7.2% of total population, It is expected to enter the aging society. As the aging issue becomes a social issue, the public's interest in the characteristics of the elderly population, the welfare of the elderly such as housing, health, culture, and leisure has increased, and the demand for statistics is also increasing. The key to this change is that chronic degenerative diseases are becoming more of a problem than acute communicable diseases, which have been the cause of death for the past 50 years due to the increase in the aging population. Among chronic degenerative diseases, cerebrovascular death is a very important disease that is the second leading cause of mortality due to single disease.
치매(dementia)는 직업, 사회생활 및 대인관계에서 정상적인 일상생활에 장애를 주는 정도로 기억장애가 있으면서 언어장애, 방향감각 상실, 계산력 저하, 성격 및 감정의 변화 등 4가지 중 1가지 이상이 나타날 때 치매로 진단된다. 치매는 정상적인 노화와는 구분해야 할 병적인 증상이며, 그 원인에 따라 알츠하이머성 치매(Alzheimer's disease), 혈관성 치매(vascular dementia), 기타 알콜 중독, 외상, 파킨슨병의 후유증이 원인이 되는 치매로 구별된다. 혈관성 치매는 주로 뇌경색 또는 뇌졸중 등이 발생하는 경우로 발병 부위 주변의 뇌세포가 손상을 입어 기억력 상실 등의 증상이 유발된다고 알려져 있다. 반면, 알츠하이머성 치매는 뇌세포 파괴에 의한 퇴행성 뇌질환으로, 초기에는 기억력 감퇴, 성격의 변화 및 사고력 저하 등의 증상을 보이며 서서히 진행되지만, 대부분의 환자는 8~10년 내에 폐렴 등으로 사망하는 것으로 알려져 있다. 최근의 역학 연구에 의하면 고혈압, 당뇨병, 고지혈증 및 심장질환 등의 뇌혈관 질환의 위험인자들이 혈관성 치매뿐만 아니라 알츠하이머성 치매의 발병률을 증가시킨다는 보고는 있었지만, 아직까지 정확한 병인이나 치료법은 알려지지 않은 실정이다.
Dementia is a disorder characterized by impairment of normal daily life in occupational, social, and interpersonal relationships, with memory impairment, dementia, disorientation, loss of comprehension, change in personality and emotions, . Alzheimer's disease, vascular dementia, and other dementias caused by alcoholism, trauma, and sequelae of Parkinson's disease, depending on the cause, is a pathological symptom that should be distinguished from normal aging. do. Vascular dementia is mainly caused by cerebral infarction or stroke. It is known that brain cells around the affected area are damaged, causing symptoms such as loss of memory. On the other hand, Alzheimer's dementia is a degenerative brain disease caused by brain cell destruction. In the early stages, it gradually progresses with symptoms such as memory decline, personality change, and lowering of thinking power, but most patients die from pneumonia within 8-10 years . Recent epidemiological studies have shown that the risk factors of cerebrovascular diseases such as hypertension, diabetes, hyperlipidemia and heart disease increase not only vascular dementia but also the incidence of Alzheimer's dementia, but the exact etiology and treatment methods are still unknown .
알츠하이머병(AD; Alzheimer's disease)은 신경세포(neuron) 상실과, 아밀로이드 전구체 단백질로부터 유래된 39-43 아미노산 펩티드인 아밀로이드 β단백질(amyloid-beta; Aβ)을 주요 구성성분으로 하는 세포외 노인성 반(senile plaque)을 특징으로 한다. 시험관 내 및 생체 내 연구 결과 Aβ 또는 Aβ 펩티드 단편은 독성 효과를 갖는 것으로 보고되어 Aβ가 AD의 발병에 중요한 역할을 함을 시사한다(Butterfield et al., Free Radical Biology and Medicine, 2002,32:1050-1060 ; ButterfIeld et al.,Free Radical Biology and Medicine, 2007, 43:658-677). 배양시, Aβ는 신경세포 사멸을 직접적으로 유도하며 신경세포를 흥분 독성 및 산화성 손상에 취약하게 한다. NMDA(N-methyl-D-aspartate receptor)수용체는 Aβ결합의 선택적 기질이나 Aβ-유발되는 글루타메이트 흥분 독성의 매개자로 작용한다. NMDA수용체는 특히 Ca2 +에 고도로 투과성인 리간드-게이트/볼티지-감수성 양이온 채널이다. [Ca2 +]i의 광범위한 상승은 직접적으로 세포 기능부전, 과잉흥분 또는 사멸에 이르게 한다. 따라서 Aβ의 신경 독성 효과가 비-경쟁적 NMDA수용체 길항제인(5R.10S)-(+)-5-메틸-10,11-디하이드로-5H-디벤조[a,d]사이클로헵텐-5,10-이민 말레이트(MK-801)[5R.10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,b)cyclohepten-5,10-imine maleate]에 의해 감소된다는 보고에 의해 증명되는 바와 같이, Aβ노출에 의한 NMDA수용체를 통한 Ca2 +유입은 Aβ-유도된 신경 독성에서 결정적인 역할을 한다. 활성산소(Reactive Oxygen species; ROS)의 형성 또한, 퇴행성 뇌질환의 발병에 관여하는 것으로 믿어진다. 몇몇 증거가 신경세포 항상성을 방해하는 광범위한 분자 적 형상을 통해 신경퇴화를 촉발하거나 용이하게 함으로써, Aβ-매개 된 신경병에서 활성 인자로서 산화성 스트레스의 관여를 뒷받침한다. 그러나 NMDA수용체 길항제와 신경세포 채널의 직접적 차단제의 임상적 유익성은, 그들이 확인할만한 효능을 결여하고 있거나 심각한 부작용을 가지므로, 논란의 여지가 있다.
Alzheimer's disease (AD) is characterized by a loss of neurons and an extracellular senescent half-life with amyloid-beta (Aβ), a 39-43 amino acid peptide derived from amyloid precursor protein senile plaque. In vitro and in vivo studies have shown that A [beta] or A [beta] peptide fragments have toxic effects, suggesting that A [beta] plays an important role in the pathogenesis of AD (Butterfield et al. , 2002 , 32: 1050 -1060; ButterfIeld et al ., Free Radical Biology and Medicine, 2007, 43: 658-677). At the time of culture, Aβ directly induces neuronal cell death and makes neuronal cells vulnerable to excitotoxic and oxidative damage. NMDA (N-methyl-D-aspartate receptor) receptors act as mediators of Aβ-binding selective substrate or Aβ-induced glutamate excitotoxicity. NMDA receptors are highly transmissive in particular ligand in Ca 2 + - gate / overvoltage - is sensitive cation channels. Extensive increase in [Ca 2 +] i will lead directly to cell dysfunction, over-excitement or death. Thus, the neurotoxic effect of A? Is a noncompetitive NMDA receptor antagonist (5R.10S) - (+) - 5-methyl-10,11-dihydro-5H- dibenzo [a, d] cycloheptene- -Imine maleate (MK-801) [5R.10S) - (+) - 5-methyl-10,11-dihydro-5H-dibenzo (a, b) cyclohepten-5,10-imine maleate] as will be demonstrated by the report, Ca + 2 influx through NMDA receptors by exposure Aβ plays a crucial role in the neurotoxicity induced Aβ-. The formation of reactive oxygen species (ROS) is also believed to be involved in the onset of degenerative brain diseases. Some evidence supports the involvement of oxidative stress as an active factor in A [beta] -mediated neuropathy by triggering or facilitating neurodegeneration through a broad molecular shape that interferes with neuronal homeostasis. However, the clinical benefit of direct blockers of NMDA receptor antagonists and neuronal channels is controversial, as they lack the verifiable efficacy or have serious adverse effects.
정상인들도 나이가 들면 어느 정도의 기억장애를 겪게 되지만, 알츠하이머 환자들에게 특이적으로 나타나는 성격변화 등의 증상은 나타나지 않게 되는데, 이를 경도인지장애(MCI; Mild cognitive impairment)라 한다. 경도인지장애는 알츠하이머 질환의 전구증상으로 여겨지고, 단기기억상실, 공간기억상실 및 감정적 불균형으로 특징지어지는데, 이는 다시 몇 단계로 분류가 이루어지게 된다. 이중 기억손실과 관련된 MCI를 망각성 MCI(amnestic MCI)라 하는데, 65세 정상인이 특정 기간 안에 알츠하이머성 환자로 변환된 확률이 1 내지 3% 인데 반해, 망각성 MCI를 가진 그룹은 10명 중 8명이 알츠하이머성 환자로 전환되는 것으로 나타나, 망각성 경도인지장애를 가진 경우, 알츠하이머성 치매로 발전할 가능성이 높은 것으로 여겨지고 있다.
Normal people also experience some degree of memory impairment as they get older, but they do not have symptoms such as personality changes that are specific to Alzheimer's patients. This is called MCI (Mild cognitive impairment). Mild cognitive impairment is considered to be a precursor to Alzheimer's disease, characterized by short-term memory loss, spatial memory loss and emotional imbalance, which are again classified in several stages. MCI associated with dual memory loss is referred to as amnestic MCI. The probability that a normal 65-year-old is converted to an Alzheimer's patient within a certain period of time is 1 to 3%, whereas a group with oblivious MCI accounts for 8 of 10 Are converted into Alzheimer's patients, and it is believed that they are likely to develop Alzheimer ' s dementia if they have obsessive-compulsive mild cognitive impairment.
파킨슨병(Parkinson's disease)은 안정떨림, 경직, 운동완만 및 자세 불안정이 특징적으로 나타나는 신경계의 만성 진행성 퇴행성 질환으로 뇌의 흑질(Substantia Nigra pars compacta: SNc)에 분포하는 도파민의 신경세포가 점차 소실되는 신경병리학적인 특징을 나타낸다(Calne et al., 1983, Heikkila 1984). 파킨슨병 환자는 대략 60세 이상에서 인구의 약 1% 정도로 추정된다. 파킨슨병의 원인은 정확히 밝혀져 있지 않지만 유전적 인자와 환경적 인자가 서로 상호작용하여 일어난다는 '다인성 가설'이 가장 보편적으로 받아들여지고 있다. 대부분의 파킨슨병 환자들은 가족력 없이 발병하지만 약 10% 정도가 가족성 파킨슨병으로 나타나고 있다.Parkinson's disease is a chronic progressive degenerative disease of the nervous system characterized by stable tremor, stiffness, gait, and postural instability, which results in gradual loss of dopaminergic neurons in the subcortical nigra pars compacta (SNc) of the brain Exhibits neuropathologic features (Calne meat al ., 1983, Heikkila 1984). Patients with Parkinson's disease are estimated to be approximately 1% of the population at approximately 60 years of age or older. Although the cause of Parkinson's disease is not clear, the 'multinomial hypothesis' that genetic and environmental factors interact with each other is the most commonly accepted. Most patients with Parkinson's disease develop without familial involvement, but about 10% are familial Parkinson's.
파킨슨병의 감소된 도파민의 양을 증가시키기 위한 대증요법제로서 L-Dopa가 현재 일반적으로 사용되고 있다. L-Dopa는 사용 후, 파킨슨병의 진행을 더디게 하고 임상증상의 경감을 보이지만, 장기간 복용 시 불수의적인 운동, 구토 등의 부작용이 따른다(Clarke and Deane, 2001). 그 외에도, 파킨슨병을 치료하기 위하여 사용되고 있는 치료제로는 FDA 허가된 도파민 작용제(Dopamine Agonists), 카테콜-0-메틸트랜스퍼레이즈(catechol-O-methyltransferase inhibitor, COMT inhibitor), 모노아민 산화효소 B(monoamine oxidase B, MAO-B inhibitors), 항-콜린작용제(Anti-cholinergics) 등이 있다. 파킨슨병 연구를 위하여 사용되는 동물모델로는 6-하이드록시도파민(6-hydroxydopamine, 6-OHDA), 로테논(rotenon), 1-메틸-4-페닐-1,2,3,6-테트라하이드로피리딘(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP)을 이용한 동물모델이 있다. 그 중, MPTP는 1982년 마약 중독자들에 의해 인간에게서 파킨슨병을 유발시키는 것으로 처음 알려졌는데 이는 사람뿐만 아니라 영장류와 마우스에서도 임상적으로 유사한 임상증세를 나타내어 파킨슨병의 병태 생리학적인 변화를 연구하는데 적절한 실험동물모델로 평가되고 있다. MPTP에 의한 도파민 신경 세포의 손상 기전은 아직 명확하게 밝혀져 있지 못하나 최근에는 MPTP 노출에 의해 대뇌에서 염증 반응(inflammation)이 증가하고, 이러한 염증반응은 파킨슨병의 병리학적 연구에 중요한 과정이라고 보고되어 있다. MPTP는 마우스와 원숭이에서 흑선조체(nigrostriatal pathway)의 급성 퇴화(acute degeneration)를 유발하므로 유용한 파킨슨 모델로 사용되어왔다. 또한, MPTP에 의한 동물 실험 모델은 파킨슨병의 급성 염증 단계로서 미토콘드리아의 기능 손상과 산화적 스트레스(oxidative stress)로 인한 세포 사멸에 대한 치료기술이나 약물의 신경보호 효과 유무를 연구하기에 적합하다고 알려져 있다.
L-Dopa is currently commonly used as a symptomatic remedy to increase the amount of reduced dopamine in Parkinson's disease. Although L-Dopa slows the progression of Parkinson's disease and alleviates clinical symptoms after use, long-term adverse effects include involuntary exercise and vomiting (Clarke and Deane, 2001). In addition, therapeutic agents used to treat Parkinson's disease include FDA-approved dopamine agonists, catechol-O-methyltransferase inhibitors (COMT inhibitors), monoamine oxidase B monoamine oxidase B, MAO-B inhibitors, and anti-cholinergics. Animal models used for the study of Parkinson's disease include 6-hydroxydopamine (6-OHDA), rotenon, 1-methyl-4-phenyl-1,2,3,6-tetrahydro There is an animal model using pyridine (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP). Among them, MPTP was first known to induce Parkinson's disease in humans by drug addicts in 1982, which is clinically similar to both humans as well as to humans in primates and mice, and is suitable for studying the pathophysiological changes of Parkinson's disease It has been evaluated as an experimental animal model. The mechanism of MPTP-induced dopaminergic neuronal injury has not yet been elucidated. Recently, however, MPTP exposure has been shown to increase inflammation in the cerebrum, and this inflammatory response has been reported to be an important process in pathological studies of Parkinson's disease . MPTP has been used as a useful Parkinson model since it causes acute degeneration of the nigrostriatal pathway in mice and monkeys. In addition, the animal model of MPTP is known to be suitable for studying the therapeutic effect of apoptosis due to mitochondrial dysfunction and oxidative stress as a stage of acute inflammation of Parkinson's disease or the neuroprotective effect of drugs have.
간질(epilepsy)은 단일한 간질 발작을 유발할 수 있는 원인 인자, 즉 신체적 이상이 없음에도 불구하고, 간질 발작이 반복적으로 발생하여 만성화된 질환군으로서, 신경생물학적, 정신적, 인지적, 사회적 변화를 수반한다(Robert et al., 2005). 간질의 발병률과 유병률은 생후 1년 이내에 가장 높았다가 급격히 낮아지고, 60세 이상의 노년층에서 다시 급격히 증가하는 U자 형태를 보이며, 주요 원인으로는 뇌졸중, 선천기형, 두부외상, 뇌염, 뇌종양, 퇴행성뇌병증, 유전, 미숙아, 분만 전후의 손상 등이 있다.Epilepsy is a group of chronic diseases in which epileptic seizures occur repeatedly despite the absence of a causal factor that may cause a single epileptic seizure, ie, neurological, psychological, cognitive, and social changes (Robert meat al ., 2005). The prevalence and prevalence of epilepsy are highest in the first year of life, rapidly decreasing, and suddenly increasing in the older age group of 60 years or older. The main causes are stroke, congenital anomaly, head trauma, encephalitis, brain tumor, degenerative encephalopathy , Heredity, premature infants, and damage before and after delivery.
간질 연구를 위해 사용되는 대표적인 동물실험 모델로서, 카인산(Kainic acid)로 유도된 흰 쥐 간질 모델은 카인산 수용체를 통한 신경흥분독성 및 간질 발작을 나타내며, 인지 장애 및 신경세포 손상을 수반한다.
As a representative animal experimental model used for epilepsy studies, Kainic acid-induced white rat epilepsy model shows neuroleptic toxicity and seizure attack through caffeic acid receptor, accompanied by cognitive impairment and nerve cell damage.
어성초(Houttuynia cordata THUNB.)는 삼백초과(Saururaceae)의 식물인 약모밀(Houttuynia cordata THUNB.)의 전초로, 아시아 동남부와 특히 일본, 한국 등지에 서식한다. 상기 어성초는 열 가지 약효가 있다고 하여 십약이라고도 부르며 줄기는 고구마 잎과 같고 생잎을 만지면 생선 비린내가 심하게 나는 것에서 유래되어 어성초로 부르기도 한다. 어성초는 약용, 식용으로도 가능하며 식품공전 식품 원재료분류에 부원료로 최소량만을 사용할 수 있는 동식물로 분류되어 있고 약리적으로는 강심, 이뇨, 항균, 해독, 항암 효능이 있는 것으로 널리 알려져 있으며, 민간에서는 해독과 미용을 돕는 화장품 및 건강기능식품으로 이용하고 있다. 상기 어성초에는 항균, 항바이러스, 진균억제에 효과가 있는 데카노일 아세트알데히드 화합물과 이뇨, 강심, 배변작용에 효과가 있는 플라보노이드계열의 화합물들이 많이 함유되어 있다는 것이 보고되어 있다. 특히, 본초강목에서는 해열작용과 함께 종기 독 등을 없앤다고 기록되어 있고, 중양 대사전에는 피를 맑게 해주고 염증을 없애며 소변배출을 돕는다고 쓰여있다. 한편, 어성초는 한방 및 민간요법에서 사용되는 약용식물로서, 이를 사용한 종래기술로는 대한민국 등록특허 제521813호에서 대두, 영지, 어성초, 인진쑥, 감초 등의 혼합 생약조성물을 유효성분으로 함유하는 부작용과 독성이 적고 안전하며, 항암, 면역증강 및 동맥경화 치료의 약학적 조성물 및 그의 제조방법이 기재되어 있다.
Houttuynia cordata THUNB. Is an outbreak of Houttuynia cordata THUNB., A plant of Saururaceae. It lives in southeastern Asia and especially in Japan and Korea. It is said that there are ten kinds of phytophthora, and the stem is like leaf of sweet potato. It can be used for medicinal and edible purposes. It is classified as a plant and animal which can only use the minimum amount as a supplementary ingredient in the classification of food raw materials. It is widely known that it has pharmacological effects such as strength, diuretic, antibacterial, detoxification and anti- And beauty cosmetics and health functional foods. It has been reported that the perennial herb contains decanoyl acetaldehyde compound, which is effective for antibacterial, antiviral and fungal inhibition, and a flavonoid-based compound which is effective for diuretic, cardiac, and defecatory actions. In particular, it is said that in the main river gangmyeon, it removes the poisonous poison as well as the fever, and it says that it purifies the blood, eliminates the inflammation and helps the urine discharge. On the other hand, Hwasungcho is a medicinal plant used in oriental medicine and folk remedies. As a conventional technology using it, Korea Patent No. 521813 discloses a side effect containing a mixed herbal composition such as soybean, lard, Toxic and safe, and pharmaceutical compositions of anticancer, immunostimulating and atherosclerotic therapies, and methods of making the same.
백렴(Ampelopsis japonica Makino)은 가회톱의 비대한 괴근으로, 긴 타원형 또는 방추형으로 양쪽 끝이 뾰족한 모양이다. 맛이 쓰고 성질은 차기 때문에 열을 식히고 독을 풀어주는 효능이 있다. 복용 또는 외용으로 사용하며, 청열(熱)작용으로 옹저, 종기 및 창양 등을 다스리고 새살이 돋게 하며, 악창이나 부스럼이 아물지 않거나 물이나 불로 상처를 받았을 때 새살을 돋게 하여 치료해 준다.
Ampelopsis japonica Makino is a bulbous bulb of a bivalve, long elliptical or spindle shaped with both ends pointed. It has the effect of cooling the heat and releasing the poison because it tastes and the nature is cold. It is used for taking or for external use. It is used for treating fever, boil and whitening by controlling fever (heat), raising newborn, and treating new disease when it is not healed by sores or swelling, or when it is injured by water or fire.
이에 본 발명자는 치매, 파킨슨병 또는 간질에 대한 치료 및 예방효과를 갖는 천연물질 개발에 노력하던 중, 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물은 흰 쥐의 베타아밀로이드(Amyloid-β; Abeta) 올리고머 독성 유발 모델에서 인지 개선 효과, 대뇌피질(cortical) 및 해마(hippocampal) 세포에서 베타아밀로이드(Amyloid-β) 유발 독성에 대한 세포 보호효과, SH-SY5Y 세포 및 PC12 세포에서 6-OHDA(6-hydroxydopamine) 유발 독성에 의한 세포 보호효과, 흰 쥐의 카인산(Kainic acid) 독성 유발 모델에서 인지 개선 효과 및 세포 보호효과를 확인하여 치매, 파킨슨병 또는 간질의 예방 및 치료에 유용하게 사용될 수 있음을 밝힘으로써, 본 발명을 완성하였다.
Accordingly, the present inventors have found that when a natural substance having therapeutic and preventive effects against dementia, Parkinson's disease or epilepsy is being developed, a mixture of a perennial herb extract or a perennial herb extract and a perennial herb extract may be used as an amyloid-β (Abeta) Cytoprotective effect on amyloid-beta induced toxicity in cortical and hippocampal cells, 6-OHDA (6-OHDA) in SH-SY5Y cells and PC12 cells, hydroxydopamine) -induced cytotoxicity, and the cognitive improvement effect and cytoprotective effect in a model inducing kainic acid toxicity in white rats to be useful for the prevention and treatment of dementia, Parkinson's disease or epilepsy The present invention has been completed.
본 발명의 목적은 어성초(Houttuynia cordata THUNB.) 추출물을 유효성분으로 함유하는 치매(dementia), 파킨슨병(Parkinson's disease) 또는 간질(epilepsy) 예방 및 치료용 약학적 조성물, 및 치매, 파킨슨병 또는 간질 예방 및 개선용 건강식품용 조성물을 제공하는 것이다.
It is an object of the present invention to provide a pharmaceutical composition for the prevention and treatment of dementia, Parkinson's disease or epilepsy which contains Houttuynia cordata THUNB. Extract as an active ingredient and a pharmaceutical composition for preventing and treating dementia, Parkinson's disease or epilepsy And to provide a composition for a health food for prevention and improvement.
상기 목적을 달성하기 위해서, 본 발명은 어성초(Houttuynia cordata THUNB.) 추출물을 유효성분으로 함유하는 치매(dementia) 예방 및 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention Houttuynia cordata (Houttuynia cordata THUNB.) extract as an active ingredient for the prevention and treatment of dementia.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 파킨슨병(Parkinson's disease) 예방 및 치료용 약학적 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing and treating Parkinson's disease comprising an extract of Rhododendron japonica as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 간질(epilepsy) 예방 및 치료용 약학적 조성물을 제공한다. In addition, the present invention provides a pharmaceutical composition for preventing and treating epilepsy containing an extract of Aspergillus as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴(Ampelopsis japonica Makino) 추출물의 혼합물을 유효성분으로 함유하는 치매 예방 및 치료용 약학적 조성물을 제공한다.The present invention also relates to a method for producing japonica The present invention provides a pharmaceutical composition for preventing and treating dementia, which comprises a mixture of an extract of Makino as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating Parkinson's disease, which comprises a mixture of a Psyllium husk extract and a Bacillus subtilis extract as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 간질 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating epilepsy, which comprises a mixture of a perennial herb extract and a Glycyrrhiza extract as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 치매 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for preventing and alleviating dementia comprising an extract of Aspergillus oryzae as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for prevention and improvement of Parkinson's disease comprising an extract of Rhododendron japonica as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 간질 예방 및 개선용 건강식품용 조성물을 제공한다.Also, the present invention provides a composition for health food for preventing and improving epilepsy, which comprises a perennial herb extract as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 치매 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for preventing and alleviating dementia, which comprises a mixture of a perennial herb extract and a mulberry extract as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for health food for prevention and improvement of Parkinson's disease, which comprises a mixture of Horseshoe chinensis extract and Bacillus subtilis extract as an active ingredient.
아울러, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 간질 예방 및 개선용 건강식품용 조성물을 제공한다.
In addition, the present invention provides a composition for health food for preventing and improving epilepsy, which comprises a mixture of a perennial herb extract and a Bacillus subtilis extract as an active ingredient.
본 발명의 어성초(Houttuynia cordata THUNB.) 추출물, 또는 어성초 추출물과 백렴(Ampelopsis japonica Makino) 추출물의 혼합물은 흰 쥐의 베타아밀로이드(Amyloid-β; Abeta) 올리고머 독성 유발 모델에서 인지 기능의 개선 효과를 확인하였고, 베타아밀로이드 유발 치매 모델에서 세포 보호효과 및 세포사멸 억제효과를 확인하였으며, 6-OHDA(6-hydroxydopamine) 유발 파킨슨병 모델에서 세포 보호효과를 확인하였고, 카인산(Kainic acid) 유발 간질 모델에서 세포 보호효과를 확인함으로써, 상기 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물은 치매(dementia), 파킨슨병(Parkinson's disease), 또는 간질(epilepsy) 예방 및 치료용 약학적 조성물 또는 상기 목적의 건강식품용 조성물의 개발에 효과적으로 이용될 수 있다.
In the present invention, Houttuynia cordata THUNB.) extract or Ampelopsis japonica Makino extract showed improvement in cognitive function in the amyloid-β (Abeta) oligomer toxicity induction model of white rats, and beta amyloid-induced dementia The cytoprotective effect of 6-OHDA (6-hydroxydopamine) -induced Parkinson's disease was confirmed and the cytoprotective effect of kainic acid-induced epilepsy model was confirmed , Or a mixture of a perennial herb extract and a perennial herb extract is effective for the development of a pharmaceutical composition for the prevention and treatment of dementia, Parkinson's disease, or epilepsy, or a composition for health foods, Can be used.
도 1은 흰 쥐의 베타아밀로이드(Amyloid-β; Abeta) 올리고머 독성에 대한 어성초(Houttuynia cordata THUNB.) 추출물의 인지 기능 개선 효과를 나타낸 그래프이다;
HCW: 어성초 물 추출물.
도 2는 대뇌피질(Cortical) 세포에서 어성초 추출물, 또는 어성초 추출물 및 백렴(Ampelopsis japonica Makino) 추출물의 혼합물을 처리한 후, 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물;
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
HCW: 어성초 물 추출물; 및
HCE: 어성초 에탄올 추출물.
도 3은 대뇌피질 세포에서 베타아밀로이드 독성처리에 대한 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 전처리의 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물;
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
HCW: 어성초 물 추출물; 및
HCE: 어성초 에탄올 추출물.
도 4는 해마(hippocampal)세포에서 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 처리한 후, 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물; 및
HCW: 어성초 물 추출물.
도 5는 해마 세포에서 베타아밀로이드 독성처리에 대한 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 전처리의 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물; 및
HCW: 어성초 물 추출물.
도 6은 SH-SY5Y 세포에서 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 처리한 후, 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물;
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
HCW: 어성초 물 추출물; 및
HCE: 어성초 에탄올 추출물.
도 7은 SH-SY5Y 세포에서 6-OHDA(6-hydroxydopamine) 유발 독성에 대한 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 전처리의 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물;
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
HCW: 어성초 물 추출물; 및
HCE: 어성초 에탄올 추출물.
도 8은 PC12세포에서 어성초 추출물 및 백렴 추출물의 혼합물을 처리한 후, 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물; 및
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
도 9는 PC12세포에서 6-OHDA 유발 독성에 대한 어성초 추출물 및 백렴 추출물의 혼합물 전처리의 세포 생존율을 나타낸 그래프이다;
HCW:AJW: 어성초 물 추출물 및 백렴 물 추출물의 혼합물; 및
HCE:AJE: 어성초 에탄올 추출물 및 백렴 에탄올 추출물의 혼합물;
도 10은 흰 쥐의 카인산(Kainic acid) 독성에 대한 어성초 추출물의 해마세포 보호효과를 나타낸 그래프이다;
HCW: 어성초 물 추출물.
도 11은 흰 쥐의 카인산 독성에 대한 어성초 추출물의 인지 기능 개선 효과를 나타낸 그래프이다;
HCW: 어성초 물 추출물.1 is beta amyloid (Amyloid-β; Abeta) of the rats of the Houttuynia cordata oligomer toxicity (Houttuynia cordata THUNB.) extract of the present invention;
HCW: Horsetail water extract.
FIG. 2 is a graph showing cell viability after treatment of a mixture of Houttuynia cordata extract or Houttuynia cordata extract and Ampelopsis japonica Makino extract in cortical cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori;
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
HCW: Horseshoe water extract; And
HCE: Horsetail ethanol extract.
3 is a graph showing the cell survival rate of Pretreatment of Bethel amyloid poisonous extract, or of a mixture of Betulaceae extract and Betulaceae extract, in cerebral cortical cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori;
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
HCW: Horseshoe water extract; And
HCE: Horsetail ethanol extract.
FIG. 4 is a graph showing cell viability after treatment of Horsch-like extract or Horseradime extract and horseradish peroxidase extract in hippocampal cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori; And
HCW: Horsetail water extract.
FIG. 5 is a graph showing the cell survival rate of Pretreatment of Beta amyloid Toxicity Treatment in Hippocampal Cells or Pretreatment of Pretreatment with Bark Extract;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori; And
HCW: Horsetail water extract.
FIG. 6 is a graph showing the cell survival rate after treatment of Hwasungcho extract or mixture of Hwasungcho extract and Glycyrrhiza uralensis extract in SH-SY5Y cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori;
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
HCW: Horseshoe water extract; And
HCE: Horsetail ethanol extract.
FIG. 7 is a graph showing the cell survival rate of pretreatment of 6-OHDA (6-hydroxydopamine) -induced toxic extracts of SH-SY5Y cells or mixture of Horticultural extracts and Bacillus cereus extracts;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori;
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
HCW: Horseshoe water extract; And
HCE: Horsetail ethanol extract.
8 is a graph showing the cell survival rate after treatment of a mixture of Hwasung extract and Bacillus subtilis extract in PC12 cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori; And
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
9 is a graph showing the cell survival rate of pretreatment of a mixture of Houttuynia cordata extract and Bacillus subtilis extract against 6-OHDA-induced toxicity in PC12 cells;
HCW: AJW: a mixture of water extract of Bombyx mori and extract of Bombyx mori; And
HCE: AJE: a mixture of Horseshoe Ethanol Extract and Bacillus ethanol Extract;
FIG. 10 is a graph showing the hippocampal protection effect of the perennial herb extract against the toxicity of kainic acid in white rats;
HCW: Horsetail water extract.
Fig. 11 is a graph showing the cognitive function improving effect of the Rhizoma extract on the toxicity of chitosan in the white rats;
HCW: Horsetail water extract.
이하, 본 발명을 상세히 설명한다.
Hereinafter, the present invention will be described in detail.
본 발명은 어성초(Houttuynia cordata THUNB.) 추출물을 유효성분으로 함유하는 치매(dementia) 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating dementia containing an extract of Houttuynia cordata THUNB. As an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 파킨슨병(Parkinson's disease) 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating Parkinson's disease comprising an extract of Rhododendron japonica as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 간질(epilepsy) 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating epilepsy containing an extract of Aspergillus as an active ingredient.
상기 어성초는 재배한 것 또는 시판되는 것 등 제한 없이 사용할 수 있다. The herringbone may be cultivated or commercially available.
상기 치매는 알츠하이머병(Alzheimer's disease), 혈관성 치매(vascular dementia) 또는 경도인지장애(MCI; Mild cognitive impairment)로 이루어지는 군으로부터 선택되는 어느 하나인 것이 바람직하나 이에 한정되지 않는다.The dementia is preferably any one selected from the group consisting of Alzheimer's disease, vascular dementia, and hard cognitive impairment (MCI), but is not limited thereto.
상기 어성초 추출물은 하기와 같은 단계로 제조되는 것이 바람직하나 이에 한정되지 않는다.It is preferable that the extract of Hwasungcho is prepared by the following steps, but it is not limited thereto.
1) 건조한 어성초를 추출용매를 가하여 추출하는 단계;1) extracting the dried oyster shell with an extraction solvent;
2) 단계 1)의 추출물을 여과하는 단계; 및2) filtering the extract of step 1); And
3) 단계 2)의 여과한 추출물을 감압농축하는 단계.3) Concentrating the filtered extract of step 2) under reduced pressure.
상기 방법에 있어서, 단계 1)의 추출 용매는 물, 알코올 또는 이의 혼합물, 바람직하게는 C1 내지 C2의 저급 알코올 또는 이들의 혼합 용매로부터 선택된 용매를 사용하는 것이 바람직하며, 70% 에탄올 수용액을 사용하는 것이 더욱 바람직하나, 이에 한정되는 것은 아니다. 상기 추출 용매의 양은 어성초 건조 중량의 5 내지 15배로 하는 것이 바람직하고 7 내지 10배로 하는 것이 더욱 바람직하나 이에 한정되지 않는다. 상기 추출 방법은 열수추출, 침지 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출 방법을 사용할 수 있으나 이에 한정되지 않는다. 상기 추출시 온도는 10℃ 내지 100℃인 것이 바람직하며 상온인 것이 더욱 바람직하다. 상기 추출 시간은 30분 내지 3시간이 바람직하고, 1 ~ 2시간이 더욱 바람직하나 이에 한정되지 않는다. 상기 추출 횟수는 1 ~ 5회인 것이 바람직하고 3회인 것이 더욱 바람직하나 이에 한정되지 않는다.In the above method, the extraction solvent of step 1) is preferably a solvent selected from water, an alcohol or a mixture thereof, preferably a C 1 to C 2 lower alcohol or a mixed solvent thereof, and a 70% aqueous ethanol solution But it is not limited thereto. The amount of the extraction solvent is preferably 5 to 15 times, more preferably 7 to 10 times, the dry weight of the crucian carob, but is not limited thereto. The extraction method may be an extraction method such as hot water extraction, immersion extraction, reflux cooling extraction, or ultrasonic extraction, but is not limited thereto. The extraction temperature is preferably in the range of 10 ° C to 100 ° C, more preferably room temperature. The extraction time is preferably 30 minutes to 3 hours, more preferably 1 to 2 hours, but is not limited thereto. The number of times of extraction is preferably 1 to 5 times, more preferably 3 times, but is not limited thereto.
상기 방법에 있어서, 단계 3)의 감압농축은 감압농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 동결건조하는 것이 바람직하나 이에 한정하지 않는다.
In the above method, it is preferable to use a reduced pressure concentrator or a vacuum rotary evaporator for the lowering of the pressure in step 3), but it is not limited thereto. The drying is preferably performed by lyophilization, but is not limited thereto.
본 발명자들은 어성초 추출물의 흰 쥐의 베타아밀로이드(Amyloid-β; Abeta) 올리고머 독성 유발 모델에서의 인지기능 개선 효과를 측정한 결과, 어성초 추출물의 투여에 의해 인지기능이 유의적으로 증가하여 개선 효과를 나타내는 것을 확인하였다(도 1 참조). As a result of measuring the cognitive function improving effect in the amyloid-β (Abeta) oligomer toxicity induction model of white rats, the inventors of the present invention found that the cognitive function was significantly increased (See Fig. 1).
또한, 본 발명자들은 어성초 추출물의 대뇌피질(cortical) 세포에서 세포보호효과를 확인하기 위하여, 베타아밀로이드(Amyloid-β; Abeta) 유발 독성에 따라 세포 생존율을 측정한 결과, 어성초 추출물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 2 및 도 3 참조).In addition, the present inventors measured the cell survival rate according to the amyloid-β (Abeta) -induced toxicity in order to confirm the cytoprotective effect on the cortical cells of the Houttuynia cordata extract. As a result, (Fig. 2 and Fig. 3). As shown in Fig.
또한, 본 발명자들은 어성초 추출물의 해마(hippocampal) 세포에서 세포보호효과를 확인하기 위하여, 베타아밀로이드 유발 독성에 따라 세포 생존율을 측정한 결과, 어성초 추출물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 4 및 도 5 참조).In order to confirm the cytoprotective effect of horseradish peroxidase, the present inventors measured the cell survival rate according to the beta amyloid-induced toxicity. As a result, the cell survival rate was significantly increased when the horsetail extract was treated, (See Figs. 4 and 5).
또한, 본 발명자들은 어성초 추출물의 SH-SY5Y 세포에서 세포보호효과를 확인하기 위하여, 6-OHDA(6-hydroxydopamine) 유발 독성에 대한 세포 생존율을 측정한 결과, 어성초 추출물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 6 및 도 7 참조).In addition, the present inventors measured the cell survival rate of 6-OHDA (6-hydroxydopamine) -induced toxicity in order to confirm cytoprotective effect on SH-SY5Y cells of Hwasungsik extract. As a result, the cell survival rate (Fig. 6 and Fig. 7).
아울러, 본 발명자들은 어성초 추출물의 흰 쥐의 카인산(Kainic acid) 독성 유발 모델에서의 해마세포 보호효과 및 인지기능 개선 효과를 측정한 결과, 어성초 추출물의 투여에 의해 해마세포가 유의하게 증가하였고, 인지기능이 유의적으로 증가하여 개선 효과를 나타내는 것을 확인하였다(도 10 및 도 11 참조).In addition, the present inventors measured hippocampal cell protection effect and cognitive function improving effect in a rat induced rat kainic acid toxicity model, and as a result, And the cognitive function was significantly increased to show an improvement effect (see FIGS. 10 and 11).
따라서, 본 발명의 어성초 추출물은 흰 쥐의 베타아밀로이드 올리고머 독성 유발 모델에서의 인지기능을 개선하고, 베타아밀로이드 및 6-OHDA 유발 독성에 대하여 세포를 보호하는 효과를 가지며, 카인산 유발 모델에서 세포보호효과 및 인지기능 개선 효과를 보이므로, 치매, 파킨슨병 또는 간질 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 이용될 수 있다.
Therefore, the herbal extract of the present invention has the effect of improving the cognitive function in the beta amyloid oligomer toxicity induction model of white rats, protecting cells against beta amyloid and 6-OHDA induced toxicity, Effects and cognitive function improving effects, it can be effectively used as an active ingredient of a pharmaceutical composition for the prevention and treatment of dementia, Parkinson's disease or epilepsy.
또한, 본 발명은 어성초 추출물 및 백렴(Ampelopsis japonica Makino) 추출물의 혼합물을 유효성분으로 함유하는 치매 예방 및 치료용 약학적 조성물을 제공한다.The present invention also relates to a method for producing japonica The present invention provides a pharmaceutical composition for preventing and treating dementia, which comprises a mixture of an extract of Makino as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 파킨슨병 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating Parkinson's disease, which comprises a mixture of a Psyllium husk extract and a Glycyrrhiza uralensis extract as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 간질 예방 및 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing and treating epilepsy, which comprises a mixture of a perennial herb extract and a Glycyrrhiza extract as an active ingredient.
상기 어성초 또는 백렴은 재배한 것 또는 시판되는 것 등 제한 없이 사용할 수 있다.The herringbone or bacillus can be used without limitation such as cultivated or commercially available.
상기 치매는 알츠하이머병(Alzheimer's disease), 혈관성 치매(vascular dementia) 또는 경도인지장애(MCI; Mild cognitive impairment)로 이루어지는 군으로부터 선택되는 어느 하나인 것이 바람직하나 이에 한정되지 않는다. The dementia is preferably any one selected from the group consisting of Alzheimer's disease, vascular dementia, and hard cognitive impairment (MCI), but is not limited thereto.
상기 어성초 추출물 및 백렴 추출물의 혼합물은 하기와 같은 단계로 제조되는 것이 바람직하나 이에 한정되지 않는다.Preferably, the mixture of Hwasungcho extract and Glycyrrhiza uralensis extract is prepared by the following steps, but is not limited thereto.
1) 각각의 건조한 어성초 또는 백렴을 추출용매를 가하여 추출하는 단계;1) extracting each of dried oyster shells or white beans with an extraction solvent;
2) 단계 1)의 추출물을 여과하는 단계; 2) filtering the extract of step 1);
3) 단계 2)의 여과한 추출물을 감압농축하는 단계; 및3) concentrating the filtered extract of step 2) under reduced pressure; And
3) 단계 3)에서 수득한 각각의 어성초 추출물 및 백렴 추출물을 혼합하는 단계.3) mixing each of the Horsetail extract and Bacillus anthracis extract obtained in step 3).
상기 방법에 있어서, 단계 1)의 추출 용매는 물, 알코올 또는 이의 혼합물, 바람직하게는 C1 내지 C2의 저급 알코올 또는 이들의 혼합 용매로부터 선택된 용매를 사용하는 것이 바람직하며, 70% 에탄올 수용액을 사용하는 것이 더욱 바람직하나, 이에 한정되는 것은 아니다. 상기 추출 용매의 양은 어성초 건조 중량의 5 내지 15배로 하는 것이 바람직하고 7 내지 10배로 하는 것이 더욱 바람직하나 이에 한정되지 않는다. 상기 추출 방법은 열수추출, 침지 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출 방법을 사용할 수 있으나 이에 한정되지 않는다. 상기 추출시 온도는 10℃ 내지 100℃인 것이 바람직하며 상온인 것이 더욱 바람직하다. 상기 추출 시간은 30분 내지 3시간이 바람직하고, 1 ~ 2시간이 더욱 바람직하나 이에 한정되지 않는다. 상기 추출 횟수는 1 ~ 5회인 것이 바람직하고 3회인 것이 더욱 바람직하나 이에 한정되지 않는다.In the above method, the extraction solvent of step 1) is preferably a solvent selected from water, an alcohol or a mixture thereof, preferably a C 1 to C 2 lower alcohol or a mixed solvent thereof, and a 70% aqueous ethanol solution But it is not limited thereto. The amount of the extraction solvent is preferably 5 to 15 times, more preferably 7 to 10 times, the dry weight of the crucian carob, but is not limited thereto. The extraction method may be an extraction method such as hot water extraction, immersion extraction, reflux cooling extraction, or ultrasonic extraction, but is not limited thereto. The extraction temperature is preferably in the range of 10 ° C to 100 ° C, more preferably room temperature. The extraction time is preferably 30 minutes to 3 hours, more preferably 1 to 2 hours, but is not limited thereto. The number of times of extraction is preferably 1 to 5 times, more preferably 3 times, but is not limited thereto.
상기 방법에 있어서, 단계 4)의 혼합비율은 어성초 추출물 및 백렴 추출물을 1:1 내지 10:1인 것이 바람직하고 1:1 또는 10:1인 것인 더욱 바람직하나 이에 한정되지 않는다.
In the above method, the mixing ratio of step 4) is preferably 1: 1 to 10: 1, more preferably 1: 1 or 10: 1, but is not limited thereto.
본 발명자들은 어성초 추출물 및 백렴 추출물의 혼합물의 대뇌피질(cortical) 세포에서 세포보호효과를 확인하기 위하여, 베타아밀로이드 유발 독성에 따라 세포 생존율을 측정한 결과, 어성초 추출물 및 백렴 추출물의 혼합물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 2 및 도 3 참조).The present inventors measured the cell viability according to beta amyloid-induced toxicity in order to confirm the cytoprotective effect of corticosteroids on the mixture of Horseshoe extract and Bacillus subtilis extract. As a result, And the survival rate was significantly increased to show a cytoprotective effect (see FIGS. 2 and 3).
또한, 본 발명자들은 어성초 추출물 및 백렴 추출물의 혼합물의 해마 세포에서 세포보호효과를 확인하기 위하여, 베타아밀로이드 유발 독성에 따라 세포 생존율을 측정한 결과, 어성초 추출물 및 백렴 추출물의 혼합물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 4 및 도 5 참조).In order to confirm the cytoprotective effect of horseradish on the horseradish of a mixture of Horseshoe chinensis extract and Glycyrrhiza uralensis extract, the present inventors measured the cell viability according to beta amyloid-induced toxicity and found that when the mixture of Hibiscus gigantus extract and Bacillus subtilis extract was treated, (Fig. 4 and Fig. 5).
아울러, 본 발명자들은 어성초 추출물 및 백렴 추출물의 혼합물의 SH-SY5Y 세포에서 세포보호효과를 확인하기 위하여, 6-OHDA(6-hydroxydopamine) 유발 독성에 대한 세포 생존율을 측정한 결과, 어성초 추출물을 처리하면 세포 생존율이 유의적으로 증가하여 세포보호효과를 나타내는 것을 확인하였다(도 6 및 도 7 참조).In addition, the present inventors measured the cell survival rate of 6-OHDA (6-hydroxydopamine) -induced toxicity in order to examine the cytoprotective effect of SH-SY5Y cells in the mixture of the extract of Hwasungcho And the cell survival rate was significantly increased to show a cytoprotective effect (see FIGS. 6 and 7).
따라서, 본 발명의 어성초 추출물 및 백렴 추출물의 혼합물은 베타아밀로이드 및 6-OHDA 유발 독성에 대하여 세포를 보호하는 효과를 가지므로 치매, 파킨슨병 또는 간질 예방 및 치료용 조성물의 유효성분으로 유용하게 이용될 수 있다.
Therefore, the mixture of Hwasung's extract and Glycyrrhiza extract of the present invention has an effect of protecting cells against beta-amyloid and 6-OHDA-induced toxicity, and thus is usefully used as an active ingredient of dementia, Parkinson's disease or composition for preventing and treating epilepsy .
상기 본 발명의 조성물은, 조성물 총 중량에 대하여 상기 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 0.1 내지 90 중량%로 포함하는 것이 바람직하나 이에 한정되지 않는다.Preferably, the composition of the present invention comprises 0.1 to 90% by weight of the perennial herb extract or the mixture of the perennial herb extract and the perennial herb extract, based on the total weight of the composition, but is not limited thereto.
상기 본 발명의 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the preparation of pharmaceutical compositions.
상기 본 발명의 조성물은 경구 또는 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식을 선택하는 것이 바람직하며, 이에 한정되는 것은 아니다.The composition of the present invention can be administered orally or parenterally, and it is preferable to select an external or intraperitoneal injection, intramuscular injection, subcutaneous injection, intravenous injection, intramuscular injection, But is not limited thereto.
상기 본 발명의 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 상기 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The composition of the present invention can be formulated into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to conventional methods have. Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations may contain at least one excipient, for example, starch, calcium carbonate (calcium carbonate), sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 상기 조성물은 1일 0.0001 내지 1 g/㎏으로, 바람직하게는 0.001 내지 200 ㎎/㎏으로 투여하는 것이 바람직하나 이에 한정되지 않는다. 상기 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition is preferably administered at a dose of 0.0001 to 1 g / kg per day, preferably 0.001 to 200 mg / kg per day, but is not limited thereto. The above administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 치매 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for preventing and alleviating dementia comprising an extract of Aspergillus oryzae as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for prevention and improvement of Parkinson's disease comprising an extract of Rhododendron japonica as an active ingredient.
또한, 본 발명은 어성초 추출물을 유효성분으로 함유하는 간질 예방 및 개선용 건강식품용 조성물을 제공한다.Also, the present invention provides a composition for health food for preventing and improving epilepsy, which comprises a perennial herb extract as an active ingredient.
상기 치매는 알츠하이머병(Alzheimer's disease), 혈관성 치매(vascular dementia) 또는 경도인지장애(MCI; Mild cognitive impairment)로 이루어지는 군으로부터 선택되는 어느 하나인 것이 바람직하나 이에 한정되지 않는다. The dementia is preferably any one selected from the group consisting of Alzheimer's disease, vascular dementia, and hard cognitive impairment (MCI), but is not limited thereto.
본 발명의 어성초 추출물은 베타아밀로이드 및 6-OHDA 유발 독성에 대하여 세포를 보호하는 효과를 가지며, 카인산 유발 모델에서 세포보호효과 및 인지기능 개선 효과를 보이므로 치매, 파킨슨병 또는 간질 예방 및 개선용 건강식품의 유효성분으로 유용하게 이용될 수 있다.
The herbal extract of the present invention has an effect of protecting cells against beta amyloid and 6-OHDA-induced toxicity, and exhibits a cytoprotective effect and a cognitive function improving effect in a kinetic acid-induced model. Therefore, the herbal extract of the present invention is useful for prevention and improvement of dementia, And can be usefully used as an active ingredient of health food.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 치매 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for a health food for preventing and alleviating dementia, which comprises a mixture of a perennial herb extract and a mulberry extract as an active ingredient.
또한, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 파킨슨병 예방 및 개선용 건강식품용 조성물을 제공한다.The present invention also provides a composition for health food for prevention and improvement of Parkinson's disease, which comprises a mixture of Horseshoe chinensis extract and Bacillus subtilis extract as an active ingredient.
아울러, 본 발명은 어성초 추출물 및 백렴 추출물의 혼합물을 유효성분으로 함유하는 간질 예방 및 개선용 건강식품용 조성물을 제공한다.In addition, the present invention provides a composition for health food for preventing and improving epilepsy, which comprises a mixture of a perennial herb extract and a Bacillus subtilis extract as an active ingredient.
상기 치매는 알츠하이머병(Alzheimer's disease), 혈관성 치매(vascular dementia) 또는 경도인지장애(MCI; Mild cognitive impairment)로 이루어지는 군으로부터 선택되는 어느 하나인 것이 바람직하나 이에 한정되지 않는다. The dementia is preferably any one selected from the group consisting of Alzheimer's disease, vascular dementia, and hard cognitive impairment (MCI), but is not limited thereto.
본 발명의 어성초 추출물 및 백렴 추출물의 혼합물은 베타아밀로이드 및 6-OHDA 유발 독성에 대하여 세포를 보호하는 효과를 가지므로 치매, 파킨슨병 또는 간질 예방 및 개선용 건강식품의 유효성분으로 유용하게 이용될 수 있다.
Since the mixture of the herbal extract and Bacillus subtilis extract of the present invention has an effect of protecting cells against beta amyloid and 6-OHDA-induced toxicity, it can be effectively used as an active ingredient of dementia, Parkinson's disease, or health food for the prevention and improvement of epilepsy have.
상기 식품의 종류에는 특별한 제한은 없다. 상기 식품의 예로는 드링크제, 육류, 소세지, 빵, 비스켓, 떡, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food include dairy products including drinks, meat, sausage, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, ice cream, various soups, And a combination thereof, all of which include health foods in a conventional sense.
본 발명의 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The perennial herb extract of the present invention or a mixture of perennial herb extract and perennial extract may be added directly to the food or may be used together with other food or food ingredients and suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose (for prevention or improvement). Generally, the amount of the extract in the health food may be 0.01 to 15% by weight of the total food, and the health beverage composition may be added in a proportion of 0.02 to 5 g, preferably 0.3 to 1 g, based on 100 ml have. However, in the case of long-term ingestion intended for health and hygiene purposes or health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount in the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. The health functional beverage composition of the present invention is not particularly limited as long as it contains, as an essential ingredient, the above-mentioned Hibiscus berry extract or a mixture of Hibiscus and Bacillus subtilis extracts, and various flavors or natural carbohydrates Or the like as an additional component. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above .
상기 외에 본 발명의 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 추출물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다. In addition to the above-mentioned foods, the food of the present invention may contain flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the extract of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
이하, 본 발명은 실시예, 실험예 및 제조예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail with reference to Examples, Experimental Examples and Preparation Examples.
단, 하기 실시예, 실험예 및 제조예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예, 실험예 및 제조예에 한정되는 것은 아니다.
However, the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples and Production Examples.
<< 실시예Example 1> 어성초( 1> HouttuyniaHouttuynia cordatacordata THUNBTHUNB .) 및 .) And 백렴Brittany (( AmpelopsisAmpelopsis japonicajaponica MakinoMakino ) 추출물의 제조) Preparation of extract
<1-1> 어성초 물 추출물의 제조<1-1> Preparation of water extract
정도약업사(서울)에서 구입한 어성초 100 g을 잘게 파쇄한 후, 증류수를 어성초의 10배의 양으로 하여, 100℃에서 2시간 동안 환류추출한 후, 왓트만 필터 종이 #2(Whatman filter paper #2)를 이용하여 감압여과 하였다. 여액은 건조 분말화 하였고, -20℃에서 보관하였으며, 실험시 용시조제하여 사용하였고, 수득률은 16.1%였다.
(100 g) purchased from Kagaku Pharmaceutical Co., Ltd. (Seoul) was finely crushed, and the distilled water was subjected to reflux extraction at 100 占 폚 for 10 hours in an amount of 100%, followed by filtration using Whatman filter paper # 2 ) Under reduced pressure. The filtrate was made into a dry powder, stored at -20 ° C, prepared in the test for use, and the yield was 16.1%.
<1-2> 어성초 에탄올 추출물의 제조<1-2> Preparation of ethanol extract
정도약업사(서울)에서 구입한 어성초에 100 g에 70% 에탄올 1000 mL를 가하여 24시간 동안 교반(stirring) 상태에서 침출시킨 후 왓트만 필터 종이 #2(Whatman filter paper #2)를 이용하여 여과시켰다. 여액을 50℃에서 감압 농축(Rotavapor R-200, heating bath B-490, BUCHI; Flawil, 스위스)하여 얻은 시료를 동결건조하여 -20℃에서 보관하였으며, 실험시 용시조제하여 사용하였으며, 수득률은 8.20%였다.
1000 g of 70% ethanol was added to 100 g of 70% ethanol, and the mixture was stirred for 24 hours. Then, the mixture was filtered using Whatman filter paper # 2 (manufactured by Wako Pure Chemical Industries, Ltd.) . The filtrate was concentrated under reduced pressure (Rotavapor R-200, heating bath B-490, BUCHI; Flawil, Switzerland) at 50 ° C and lyophilized and stored at -20 ° C. %.
<1-3> <1-3> 백렴Brittany 물 추출물의 제조 Preparation of water extract
상기 실시예 <1-1>과 동일한 방법으로 백렴 물 추출물을 제조하였다.
The extract of Bacillus japonica was prepared in the same manner as in Example <1-1>.
<1-4> <1-4> 백렴Brittany 에탄올 추출물의 제조 Preparation of ethanol extract
상기 실시예 <1-2>과 동일한 방법으로 백렴 에탄올 추출물을 제조하였다.
Ethanol extract was prepared in the same manner as in Example <1-2>.
<1-5> 어성초 추출물 및 ≪ 1-5 > 백렴Brittany 추출물의 혼합물의 제조 Preparation of a mixture of extracts
상기에서 실시예 <1-1> 내지 <1-4> 에서 제조한 어성초 추출물 및 백렴 추출물을 1:1 또는 10:1의 비율로 혼합하여 어성초 추출물 및 백렴 추출물의 혼합물을 제조하였다.
The mixture of the Hwasungcho extract and Bacillus japonica extract prepared in Examples <1-1> to <1-4> was mixed at a ratio of 1: 1 or 10: 1 to prepare a mixture of Hwasungcho extract and Bacillus extract.
<< 실험예Experimental Example 1> 생체 내( 1> in vivo ( inin vivovivo ) 어성초 추출물의 ) 항치매Anti-dementia 효과 확인 Check the effect
<1-1> 실험동물 준비<1-1> Preparation of experimental animals
실험동물은 수컷 ICR 마우스(8 주령, 30 내지 32 g, 대한바이오)를 분양받아 온도 23 ± 1℃, 습도 60 ± 10% 및 밤 낮을 12시간씩 조절하고 물과 일반식이를 충분히 공급하면서 7일간 동물실에서 적응시킨 후 실험에 사용하였다. 어성초 추출물은 50, 100, 또는 200 mg/kg를 10일간 하루에 한번 경구투여하고, 약물 투여 4일째 되는 날, 베타아밀로이드 올리고머를 10 μM로 뇌의 해마 내에 직접 주입하여 치매 유사모델을 유발하였다.
The experimental animals were housed in male ICR mice (8 weeks old, 30 to 32 g, Korea Biotech Co., Ltd.), conditioned at 23 ± 1 ° C, 60 ± 10% in humidity and 12 hours at night, It was adapted to the animal room and used in the experiment. On the fourth day of drug administration, 50, 100, or 200 mg / kg of Hwasungcho extract was orally administered once a day for 10 days, and beta amyloid oligomer was injected directly into the hippocampus of the brain by 10 μM to induce a dementia-like model.
<1-2> 행동 실험(<1-2> Behavioral Experiment BehavioralBehavioral testtest ))
베타아밀로이드 올리고머로 유도된 인지장애에 대한 어성초 추출물의 효과를 평가하기 위하여, 새로운 물체 인식 행동 실험(novel object recognition test)을 베타아밀로이드 올리고머 투여 후 5일째 되는 날과, 6일째 되는 날에 실시하였다. 구체적으로, 실험 첫날에는 가로 45 cm, 세로 45 cm, 높이 50 cm의 박스 안에 같은 물체 두 개를 넣어 두고, 마우스를 넣어 두 물체를 인식시키고, 다음 날 같은 박스 안에 두 개의 물체 중 한 개를 다른 모양의 물체로 바꾼 뒤, 새로운 물체에 대한 마우스의 탐색시간을 측정하였다.A novel object recognition test was conducted on day 5 and day 6 after beta amyloid oligomer administration to evaluate the effects of the Betula amyloid oligomer-induced celiac extract on cognitive impairment. Specifically, on the first day of experiment, we put two identical objects in a box of 45 cm in width, 45 cm in height, and 50 cm in height, and recognize the two objects by putting a mouse, and then one of two objects Shaped object, and then the mouse search time for the new object was measured.
그 결과, 도 1에 나타낸 바와 같이 어성초 추출물을 처리한 군은 베타아밀로이드 올리고머로 유도된 인지장애군과 비교하여 인지기능이 개선된 것을 확인하였다(도 1).
As a result, as shown in Fig. 1, it was confirmed that the cortisol extract-treated group had improved cognitive function as compared with the corticosteroid-induced corticosteroid (Fig. 1).
<< 실험예Experimental Example 2> 시험관 내( 2> In vitro inin vitrovitro ) 어성초 추출물의 ) 항치매Anti-dementia 효과 확인 Check the effect
<2-1> 대뇌피질(<2-1> Cerebral Cortex CorticalCortical )에서의 세포보호 효과 확인) To confirm cell protection effect
베타아밀로이드(Amyloid-β; Abeta)의 축적에 의하여 생성되는 아밀로이드 플라크(amyloid plaque)는 뇌에 축적되어 뇌신경 세포를 죽이는 물질로 알려져 있으며, 치매 연구에 이용되는 물질이다. Abeta(25-35)를 인위적으로 집합(aggregate) 시킨 물질을 이용하여 대뇌피질 세포에 대한 독성을 일으켜, 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물의 세포보호효과를 MTT 에세이(assay)를 이용하여 측정하였다. 구체적으로, 먼저, 스프래그 다우리 랫트(Sprague-Dawley rats)(대한 바이오, 서울)의 18일 된 태아에서 대뇌피질 부위만 분리한 뒤, 기계적으로 분해하여 세포를 획득한 후, 폴리-L-라이신(Poly-L-lysine)으로 미리 코팅한 96 웰 플라이트(well plate)에 1.5 × 104/웰로 세포를 접종한 후 7일을 배양하였다. 그 후, B27 프리신경세포 기본배지(free neurobasal media)에 상기 <실시예 1>의 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 농도별로 처리 30 분 후, 베타아밀로이드(Abeta, 8 ㎍)를 처리 또는 비-처리하여 총 24시간 배양하고, 1 mg/mL MTT처리 3시간 후, DMSO로 포르마잔(formazan)을 녹여 570 nm에서 흡광도를 측정하였다.Amyloid plaques produced by the accumulation of beta-amyloid (Abeta) are known to accumulate in the brain and kill brain cells, and are materials used in the study of dementia. Abeta (25-35) was artificially aggregated to induce toxicity to the cerebral cortex cells, and the cytoprotective effect of a mixture of Horseshoe extracts or Horseshoe extract and Bacillus extract was assayed using MTT assay Respectively. Specifically, first, the cerebral cortical region was separated from the 18-day-old embryo of Sprague-Dawley rats (Korea Biotech, Seoul) and mechanically digested to obtain cells, Cells were inoculated in a 96-well plate pre-coated with lysine (Poly-L-lysine) at 1.5 × 10 4 cells / well and cultured for 7 days. Thereafter, beta-amyloid (Abeta, 8 [mu] g) was added to the B27-free neurobasal media for 30 minutes after the treatment of the mixture of the herbal extract of Example 1, Treated or non-treated for a total of 24 hours, and after 3 hours of 1 mg / mL MTT treatment, formazan was dissolved in DMSO and absorbance was measured at 570 nm.
그 결과, 도 2 및 도 3에 나타낸 바와 같이 대뇌피질 세포에서 각각 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 단독으로 처리하였을 때, 세포 생존율에 영향을 미치지 않는 것을 확인하였다. 또한, Abeta 독성처리의 경우 세포 생존율은 대조군에 비하여 감소하였으며, 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물의 전처리 군의 경우 유의적인 세포보호효과를 나타내는 것을 확인하였다(도 2 및 도 3).
As a result, as shown in Figs. 2 and 3, it was confirmed that the cell viability was not influenced by the treatment with a mixture of the extracts of Rhododendron sphaeroa and Rhododendron sulphate extract and Corynebacterium glutinosa extract separately in cerebral cortical cells. In addition, the cell survival rate in the case of Abeta toxicity treatment was decreased as compared with that of the control group, and it was confirmed that the pretreatment group of Horticultural extracts or a mixture of Horticultural extracts and Bacillus subtilis extract showed significant cytoprotective effects (FIGS. 2 and 3).
<2-2> 해마(<2-2> Seahorse ( hippocampalhippocampal )에서의 세포보호 효과) On cell protection effect
어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물의 세포보호 효과를 확인하기 위해, 스프래그 다우리 랫트(대한 바이오, 서울)의 18일 된 태아에서 해마부위만 분리한 뒤, 기계적으로 분해하여 세포를 획득한 후, 폴리-L-라이신으로 미리 코팅한 96 웰 플라이트에 1.5 × 104/웰로 세포를 접종한 후 7일을 배양하였다. 그 후, B27 프리 신경세포 기본 배지에 상기 <실시예 1>의 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 농도별로 처리 30 분 후, 베타아밀로이드(Abeta, 8 ㎍)를 처리 또는 비-처리하여 총 24시간 배양하고, 1mg/mL MTT처리 3시간 후, DMSO로 포르마잔을 녹여 570 nm에서 흡광도를 측정하였다. In order to confirm the cytoprotective effect of a mixture of Hwasungcho extract and Hwasungcho extract and Bacillus extract, only the hippocampus was isolated from the 18-day-old fetus of Sprague Dawaur rats (Korea Bio, Seoul) After the cells were inoculated in a 96-well flight previously coated with poly-L-lysine at 1.5 x 10 < 4 > / well, cells were cultured for 7 days. Thereafter, the B27-free neuron basal medium was treated with a combination of the above-mentioned Houttuyia cordata extract of Example 1 or a mixture of Houttuynia cordata extract and Glycyrrhiza uralensis extract at a concentration of 30 minutes, followed by treatment or non-treatment of beta amyloid (Abeta, 8 ㎍) For 24 hours. After 3 hours of treatment with 1 mg / mL MTT, formazan was dissolved in DMSO and the absorbance was measured at 570 nm.
그 결과, 도 4 및 도 5에 나타낸 바와 같이 해마 세포에서 각각 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 단독으로 처리하였을 때 세포 생존율에는 아무런 영향을 미치지 않는 것을 확인하였다. 또한, Abeta 독성처리의 경우 세포 생존율은 대조군에 비하여 감소하였으며, 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 전처리 군의 경우 유의적인 세포보호효과를 나타내는 것을 확인하였다(도 4 및 도 5).
As a result, as shown in FIG. 4 and FIG. 5, it was confirmed that the cell viability was not affected when the horseradish peroxidase extract or the mixture of the herbal extract and the herbal extract were separately treated. In addition, the cell survival rate of Abeta toxicity treatment was decreased compared with that of the control group, and it was confirmed that the pretreatment group of Hwasungcho extract or mixture of Hwasungcho extract and Bacillus thuringiens extract showed significant cytoprotective effect (FIGS. 4 and 5).
<< 실험예Experimental Example 3> 시험관 내 어성초 추출물의 3> In vitro testosterone extract 항파킨슨병Anti-Parkinson's disease 효과 확인 Check the effect
<3-1> <3-1> SHSH -- SY5YSY5Y 세포에서 어성초 추출물의 세포 보호효과 Cytoprotective effect of Hwasungcho extract on cell
주입한 부위에 도파민 신경계 병변을 일으키는 6-OHDA(6-hydroxydopamine) 유발 독성에 대한 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물의 세포 생존율을 확인하기 위해, 도파민을 분비하는 섬유아세포종 SH-SY5Y 세포를 96 웰 플라이트에 2x104/웰로 접종한 후 2일을 배양하고, FBS 프리 DMEM 배지에 녹인 각각의 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물을 농도별로 전처리한 후, 6-OHDA를 처리 또는 비처리하여 배양하였다. 반응이 끝난 세포에 MTT 1 mg/mL 농도로 3시간 처리한 후, DMSO로 포르마잔을 녹여 570 nm에서 흡광도를 측정하였다. In order to confirm the cell survival rate of 6-OHDA (6-hydroxydopamine) -induced toxicity of a herbal extract or a mixture of herbal extracts and herringbone extracts, which causes dopaminergic lesions in the injected area, fibroblast-like SH-SY5Y cells Were inoculated in 96-well fl ows at 2 × 10 4 / well and cultured for 2 days. Each of the Horseshoe extracts or the mixture of Horseshoe extract and Bacillus extract dissolved in FBS-free DMEM medium was pretreated by concentration and then treated with 6-OHDA Non-treated and cultured. After the reaction was completed, the cells were treated with MTT at a concentration of 1 mg / mL for 3 hours, and the formazan was dissolved in DMSO to measure the absorbance at 570 nm.
그 결과, 도 6 및 도 7에 나타낸 바와 같이, SH-SY5Y 세포에서 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 단독으로 처리한 결과, 세포 생존율에는 영향을 미치지 않았으며, 어성초 추출물, 또는 어성초 추출물과 백렴 추출물의 혼합물 전처리는 6-OHDA 독성에 대하여 유의적인 세포보호효과 나타내는 것을 확인하였다(도 6 및 도 7).
As a result, as shown in FIG. 6 and FIG. 7, the treatment with SHS-SY5Y cells alone or a mixture of Horseshoe extract and Glycyrrhiza uralensis extract did not affect cell survival rate, And Bacillus thuringiensis showed significant cytoprotective effects against 6-OHDA toxicity (FIGS. 6 and 7).
<3-2> <3-2> PC12PC12 세포에서 어성초 추출물의 세포 보호효과 Cytoprotective effect of Hwasungcho extract on cell
주입한 부위에 도파민 신경계 병변을 일으키는 6-OHDA 유발 독성에 대한 어성초 추출물과 백렴 추출물의 혼합물의 세포 생존율을 확인하기 위해, 신경세포와 유사한 분화과정을 가지는 PC12 세포를 96 웰 플라이트에 1.5 x 104/웰로 접종한 후 2일을 배양하고, FBS 프리 RPMI 배지에 희석된 어성초 추출물과 백렴 추출물의 혼합물을 농도별로 처리 1시간 후, 6-OHDA(50 ㎛)를 처리 또는 비처리하여 총 4시간 배양하였다. 반응이 끝난 세포에 MTT 1 mg/mL 농도로 3시간 처리한 후, DMSO로 포르마잔을 녹여 570 nm에서 흡광도를 측정하였다. In order to confirm the cell survival rate of the mixture of Hwasungcho extract and Glycyrrhiza uralensis extract on the 6-OHDA-induced toxicity causing the dopaminergic lesion in the injected area, PC12 cells having differentiation process similar to neurons were injected into a 96-well fl ow with 1.5 x 10 4 / Well and cultured for 2 days. After 1 hour of treatment with the mixture of the Horseshoe extract and Bacillus extract diluted in FBS-free RPMI medium, 6-OHDA (50 占 퐉) was treated or not treated for a total of 4 hours Respectively. After the reaction was completed, the cells were treated with MTT at a concentration of 1 mg / mL for 3 hours, and the formazan was dissolved in DMSO to measure the absorbance at 570 nm.
그 결과, 도 8 및 도 9에 나타낸 바와 같이, PC12 세포에서 어성초 추출물과 백렴 추출물의 혼합물 단독으로 처리한 결과, 세포 생존율에는 영향을 미치지 않았으며, 어성초 추출물과 백렴 추출물의 혼합물 전처리는 6-OHDA 독성에 대하여 유의적인 세포보호효과 나타내는 것을 확인하였다(도 8 및 도 9).
As a result, as shown in FIG. 8 and FIG. 9, the cell survival rate of PC12 cells alone was not affected by the mixture of Hwasung extract and Bacillus subtilis extract. And showed significant cytoprotective effects against toxicity (Figs. 8 and 9).
<< 실험예Experimental Example 4> 생체 내( 4> in vivo inin vivovivo ) 어성초 추출물의 ) 항간질Epilepsy 효과 확인 Check the effect
<4-1> 실험동물 준비<4-1> Preparation of experimental animals
실험동물은 수컷 ICR 마우스(10 주령, 34 내지 36 g, 대한바이오)를 분양받아 온도 23 ± 1℃, 습도 60 ± 10% 및 밤 낮을 12시간씩 조절하고 물과 일반식이를 충분히 공급하면서 7일간 동물실에서 적응시킨 후 실험에 사용하였다. 어성초 추출물은 200 mg/kg를 3일간 하루에 한번 경구투여하고, 약물 투여 3일째 되는 날, 카인산(Kainic acid) 0.4 μg을 뇌의 측뇌실에 직접 주입하여 간질 유사모델을 유발하였다.
The experimental animals were housed in male ICR mice (10 weeks old, 34 to 36 g, Korea Biotech Co., Ltd.), conditioned at 23 ± 1 ° C, 60 ± 10% in humidity and 12 hours at night, It was adapted to the animal room and used in the experiment. On the third day of drug administration, 0.4 mg of kainic acid was injected directly into the lateral ventricles of the brain to induce an epileptic-like model.
<4-2> 행동 실험(<4-2> Behavioral Experiment BehavioralBehavioral testtest ))
카인산으로 유도된 인지장애에 대한 어성초 추출물의 효과를 평가하기 위하여, 새로운 물체 인식 행동 실험(novel object recognition test)을 카인산 투여 후 4일째 되는 날에 실시하였다. 구체적으로, 실험 첫날에는 가로 45 cm, 세로 45 cm, 높이 50 cm의 박스 안에 같은 물체 두 개를 넣어 두고, 마우스를 넣어 두 물체를 인식시키고, 다음날 같은 박스 안에 두 개의 물체 중 한 개를 다른 모양의 물체로 바꾼 뒤, 새로운 물체에 대한 마우스의 탐색시간을 측정하였다.A novel object recognition test was conducted on the fourth day after caffeic acid administration in order to evaluate the effect of Rhizoctonia sulphate extract on caffeic acid-induced cognitive impairment. Specifically, on the first day of experiment, two objects were placed in a box of 45 cm in length, 45 cm in height, 50 cm in height, and two objects were recognized by inserting a mouse. In the same box the next day, , And then the mouse search time for the new object was measured.
그 결과, 도 11에 나타낸 바와 같이 어성초 추출물을 처리한 군은 카인산으로 유도된 인지장애군과 비교하여 인지기능이 개선된 것을 확인하였다(도 11).
As a result, as shown in Fig. 11, it was confirmed that cognitive function was improved as compared with the cognate disorder group induced by chrysophonic acid (Fig. 11).
<4-3> 어성초 추출물의 해마세포 보호효과 확인<4-3> Confirmation of Hippocampal Protection Effect of Hwasungcho Extract
어성초 추출물의 카인산에 유도된 해마세포 손상에 대한 보호효과를 확인하기 위하여 니슬염색(Nissl staining)을 수행하였다. 구체적으로 상기 실험예 <4-2>의 행동실험을 마친 후 조직을 적출한 뒤 각 군의 마우스를 마취하여 관류 및 4% PFA로 뇌조직을 고정하였다. 후고정과정을 거친 뇌조직은 동결박편기를 이용하여 30 ㎛ 두께로 절편하고 해마 부분의 조직을 니슬염색하여 어성초 추출물의 보호효과를 분석하였다.Nissl staining was carried out in order to confirm the protective effect of kelp extract on hippocampal damage induced by hippocampus. Specifically, after the behavioral experiment of Experimental Example < 4-2 > was completed, tissues were extracted, and mice of each group were anesthetized and perfused with brain tissue fixed with 4% PFA. Brain tissues that had undergone post - fixation procedure were cut into 30 ㎛ thickness using a freezing flap machine and the protective effect of Houttuynia cordata extract was analyzed by nissl staining tissue of hippocampus.
그 결과, 도 10에 나타낸 바와 같이, 카인산으로 유도된 해마세포 손상에 대하여 어성초 추출물 200 mg/kg 전처리는 해마세포의 손실을 억제하여 세포보호효과를 나타내는 것을 확인하였다(도 10).
As a result, as shown in Fig. 10, it was confirmed that pretreatment with 200 mg / kg of Hwasungcho extract against the hippocampal-induced hippocampal damage suppresses the loss of hippocampal cells and shows a cytoprotective effect (Fig. 10).
<< 제조예Manufacturing example 1> 약학적 제제의 제조 1> Preparation of pharmaceutical preparations
<1-1> <1-1> 산제의Sanje 제조 Produce
실시예<1-1> 어성초 추출물 2 gExample < 1-1 > A mixture of 2 g
유당 1 gLactose 1 g
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.
The above components were mixed and packed in airtight bags to prepare powders.
<1-2> 정제의 제조<1-2> Preparation of tablets
실시예<1-1>의 어성초 추출물 100 ㎎100 mg of Horseshoe chinensis extract of Example < 1-1 >
옥수수전분 100 ㎎
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.
After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
<1-3> 캡슐제의 제조≪ 1-3 > Preparation of capsules
실시예<1-5>의 어성초 추출물 100 ㎎100 ㎎ of Hwasungcho extract of Example <1-5>
옥수수전분 100 ㎎
유 당 100 ㎎100 mg of milk
스테아린산 마그네슘 2 ㎎2 mg of magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.
After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.
<1-4> 환의 제조≪ 1-4 >
실시예<1-5>의 어성초 추출물 1 g1 g of Houttuynia cordifolia extract of Example < 1-5 >
유당 1.5 gLactose 1.5 g
글리세린 1 gGlycerin 1 g
자일리톨 0.5 g0.5 g of xylitol
상기의 성분을 혼합한 후, 통상의 방법에 따라 1 환 당 4 g이 되도록 제조하였다.
After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.
<1-5> 과립의 제조<1-5> Preparation of granules
실시예<1-1>의 어성초 추출물 150 ㎎150 mg of the Houttuynia cordifolia extract of Example < 1-1 >
대두 추출물 50 ㎎Soybean extract 50 mg
포도당 200 ㎎200 mg of glucose
전분 600 ㎎600 mg of starch
상기의 성분을 혼합한 후, 30% 에탄올 100 ㎎을 첨가하여 섭씨 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.
After mixing the above components, 100 mg of 30% ethanol was added and the mixture was dried at 60 캜 to form granules, which were then filled in a capsule.
<< 제조예Manufacturing example 2> 식품의 제조 2> Manufacturing of food
본 발명의 어성초 추출물을 포함하는 식품들은 다음과 같이 제조하였다.Foods containing the herbal extract of the present invention were prepared as follows.
<2-1> 밀가루 식품의 제조<2-1> Production of flour food
실시예<1-2>의 어성초 추출물 0.5 ~ 5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하였다.
0.5-5.0 parts by weight of the extract of Hwasungcho of Example <1-2> was added to wheat flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture.
<2-2> <2-2> 스프soup 및 육즙( And juicy ( graviesgravies )의 제조)
실시예<1-2>의 어성초 추출물 0.1 ~ 5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.
0.1 to 5.0 parts by weight of the extract of the herbal composition of Example < 1-2 > was added to the soup and the juice to prepare a health promotion meat product, noodle soup and juice.
<2-3> 그라운드 <2-3> Ground 비프(ground beef)의Beef 제조 Produce
실시예<1-1>의 어성초 추출물 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.
A ground beef for health promotion was prepared by adding 10 parts by weight of the Houttuynia cordifolia extract of Example <1-1> to ground beef.
<2-4> 유제품(<2-4> Dairy products ( dairydairy productsproducts )의 제조)
실시예<1-1>의 어성초 추출물 5 ~ 10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.
5 to 10 parts by weight of an adult herbal extract of Example <1-1> were added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
<2-5> <2-5> 선식의Solar 제조 Produce
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.
실시예<1-1>의 어성초 추출물을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다.The dried extract of Example 1-I was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and dried in a hot air drier, and pulverized to a size of 60 mesh with a pulverizer to obtain a dry powder.
상기에서 제조한 곡물류, 종실류 및 실시예<1-1>의 어성초 추출물을 다음의 비율로 배합하여 제조하였다:The grains, seeds, and hull extract of Example <1-1> prepared above were blended in the following proportions:
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),(30 parts by weight of brown rice, 15 parts by weight of yulmu, 20 parts by weight of barley)
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight of perilla, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds)
실시예<1-1>의 어성초 추출물(3 중량부),(3 parts by weight) of Example 1 < 1-1 >
영지(0.5 중량부), 및(0.5 parts by weight), and
지황(0.5 중량부).
Rhubarb (0.5 parts by weight).
<< 제조예Manufacturing example 3> 음료의 제조 3> Manufacturing of beverage
<3-1> <3-1> 건강음료의Health drink 제조 Produce
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 실시예<1-2>의 어성초 추출물 5 g을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 제조하였다.
(5%) of the herbal extract of Example < 1-2 > were homogeneously mixed with a supplementary material such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), And then sterilized and packaged in glass bottles, plastic bottles, etc.
<3-2> 야채 주스의 제조<3-2> Preparation of vegetable juice
실시예<1-1>의 어성초 추출물 5 g을 토마토 또는 당근 주스 1,000 ㎖에 가하여 야채 주스를 제조하였다.
Vegetable juice was prepared by adding 5 g of the oat seed extract of Example <1-1> to 1,000 ml of tomato or carrot juice.
<3-3> 과일 주스의 제조<3-3> Production of fruit juice
실시예<1-1>의 어성초 추출물 1 g을 사과 또는 포도 주스 1,000 ㎖ 에 가하여 과일 주스를 제조하였다.A fruit juice was prepared by adding 1 g of the extract of Allium cepa L. in Example <1-1> to 1,000 ml of apple or grape juice.
Claims (18)
A pharmaceutical composition for preventing and treating epilepsy containing extract of Houttuynia cordata THUNB. As an active ingredient.
The pharmaceutical composition according to claim 1, wherein the extract is extracted with water, a C 1 to C 2 lower alcohol, or a mixture thereof.
The pharmaceutical composition according to claim 2, wherein the lower alcohol is ethanol or methanol.
A pharmaceutical composition for the prevention and treatment of epilepsy, comprising a mixture of a perennial herb extract and an extract of Ampelopsis japonica Makino as an active ingredient.
[Claim 5] The pharmaceutical composition for preventing and treating epilepsy according to claim 4, wherein the mixture of the herbal extract and the Glycyrrhiza extract is mixed at a weight ratio of 1: 1 to 10: 1.
A pharmaceutical composition for preventing and treating dementia comprising water as an active ingredient, C 1 to C 2 lower alcohol, or a mixed extract thereof.
The method according to claim 6, wherein the dementia is any one selected from the group consisting of Alzheimer's disease, vascular dementia, or MCI (Mild cognitive impairment). A pharmaceutical composition.
Wherein the extract is extracted with water, a C 1 to C 2 lower alcohol, or a mixture thereof.
[Claim 9] The pharmaceutical composition for preventing and treating dementia according to claim 8, wherein the mixture of the extracts of Hwasung juice extract and Gwangju extract is mixed at a weight ratio of 1: 1 to 10: 1.
A pharmaceutical composition for the prevention and treatment of Parkinson's disease, which comprises water as an active ingredient, C 1 to C 2 lower alcohol, or a mixed extract thereof as an active ingredient.
Wherein the extract is a mixture of water extract, Cassia thunbergii extract and Bacillus subtilis extract, and the extract is extracted with water, C 1 to C 2 lower alcohol, or a mixture thereof.
[Claim 12] The pharmaceutical composition for preventing and treating Parkinson's disease according to claim 11, wherein the mixture of the Rhizoma extract and Bacillus subtilis extract is mixed at a weight ratio of 1: 1 to 10: 1.
A composition for health food for the prevention and improvement of epilepsy containing an extract of Aspergillus as an active ingredient.
A composition for a health food for prevention and improvement of epilepsy, comprising a mixture of a perennial herb extract and a Bacillus subtilis extract as an active ingredient.
A composition for a health food for preventing or ameliorating dementia, which contains water as an active ingredient, C 1 to C 2 lower alcohol, or a mixed extract thereof.
A composition for a health food for the prevention and / or alleviation of dementia, which comprises a mixture of an Aspergillus oryzae extract and a Bacillus subtilis extract as an active ingredient and the extract is extracted with water, a C 1 to C 2 lower alcohol or a mixture thereof.
A composition for a health food for prevention and improvement of Parkinson's disease, which contains water as an active ingredient, C 1 to C 2 lower alcohol, or a mixed extract thereof.
A composition for a health food for prevention and improvement of Parkinson's disease, which comprises as an active ingredient a mixture of an extract of Allium cepa L. and Bacillus subtilis, and the extract is extracted with water, a C 1 to C 2 lower alcohol, or a mixture thereof.
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CN105616661A (en) * | 2016-02-24 | 2016-06-01 | 杨晓婷 | Traditional Chinese medicine composition for treating Parkinson's disease and preparation method and application thereof |
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KR19980038121A (en) * | 1996-11-21 | 1998-08-05 | 박정주 | Method of manufacturing functional foods (materials) mainly containing fish vinegar and seaweed |
KR20020015540A (en) * | 2000-08-22 | 2002-02-28 | 김상근 | Food materials for preventing dementia and foods using the same |
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EP4582091A1 (en) * | 2024-01-05 | 2025-07-09 | Fu Jen Catholic University | Pharmaceutical combination for preventing or treating epileptic seizure and the use thereof |
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US20140220166A1 (en) | 2014-08-07 |
KR20130039547A (en) | 2013-04-22 |
CN103987395A (en) | 2014-08-13 |
WO2013055127A3 (en) | 2013-07-04 |
CN103987395B (en) | 2019-02-12 |
US9861674B2 (en) | 2018-01-09 |
WO2013055127A2 (en) | 2013-04-18 |
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